Medical Specialties Commons^™

Zone 1 Endovascular Balloon Occlusion Of The Aorta Vs Resuscitative Thoracotomy For Patient Resuscitation After Severe Hemorrhagic Shock, Alexis L Cralley, Navin Vigneshwar, Ernest E Moore, Joseph Dubose, Megan L Brenner, Angela Sauaia, Aast Aorta Study Group

Faculty, Staff and Student Publications

IMPORTANCE: Aortic occlusion (AO) is a lifesaving therapy for the treatment of severe traumatic hemorrhagic shock; however, there remains controversy whether AO should be accomplished via resuscitative thoracotomy (RT) or via endovascular balloon occlusion of the aorta (REBOA) in zone 1.

OBJECTIVE: To compare outcomes of AO via RT vs REBOA zone 1.

DESIGN, SETTING, AND PARTICIPANTS: This was a comparative effectiveness research study using a multicenter registry of postinjury AO from October 2013 to September 2021. AO via REBOA zone 1 (above celiac artery) was compared with RT performed in the emergency department of facilities experienced in both procedures …

Cost Of Failure To Achieve Textbook Outcomes: Association Of Insurance Type With Outcomes And Cumulative Cost For Inpatient Surgery, Michael A Jacobs, Jeongsoo Kim, Jasmine C Tetley, Susanne Schmidt, Bradley B Brimhall, Virginia Mika, Chen-Pin Wang, Laura S Manuel, Paul Damien, Paula K Shireman

Faculty, Staff and Student Publications

Background: Surgical outcome/cost analyses typically focus on single outcomes and do not include encounters beyond the index hospitalization.

Study design: This cohort study used NSQIP (2013-2019) data with electronic health record and cost data risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status, and operative stress assessing cumulative costs of failure to achieve textbook outcomes defined as absence of 30-day Clavien-Dindo level III and IV complications, emergency department visits/observation stays (EDOS), and readmissions across insurance types (private, Medicare, Medicaid, uninsured). Return costs were defined as costs of all 30-day emergency department visits/observation stays and readmissions.

Results: Cases were performed …

Middle Meningeal Artery Embolization For Chronic Subdural Hematomas With Concurrent Antithrombotics, Juan Carlos Martinez-Gutierrez, Hussein A Zeineddine, Michael I Nahhas, Matthew J Kole, Youngran Kim, Hyun Woo Kim, Salvatore A D'Amato, Peng Roc Chen, Spiros L Blackburn, Gary Spiegel, Sunil A Sheth, Ryan S Kitagawa, Mark J Dannenbaum

Faculty, Staff and Student Publications

BACKGROUND: Chronic subdural hematoma (CSDH) is an increasingly prevalent disease in the aging population. Patients with CSDH frequently suffer from concurrent vascular disease or develop secondary thrombotic complications requiring antithrombotic treatment.

OBJECTIVE: To determine the safety and impact of early reinitiation of antithrombotics after middle meningeal artery embolization for chronic subdural hematoma.

METHODS: This is a single-institution, retrospective study of patients who underwent middle meningeal artery (MMA) embolizations for CSDH. Patient with or without antithrombotic initiation within 5 days postembolization were compared. Primary outcome was the rate of recurrence within 60 days. Secondary outcomes included rate of reoperation, reduction in …

Safety And Tolerability Of Ser-109 As An Investigational Microbiome Therapeutic In Adults With Recurrent Clostridioides Difficile Infection: A Phase 3, Open-Label, Single-Arm Trial, Matthew D Sims, Sahil Khanna, Paul Feuerstadt, Thomas J Louie, Colleen R Kelly, Edward S Huang, Elizabeth L Hohmann, Elaine E L Wang, Caterina Oneto, Stuart H Cohen, Charles S Berenson, Louis Korman, Christine Lee, Bret Lashner, Colleen S Kraft, Mayur Ramesh, Michael Silverman, Darrell S Pardi, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke

Faculty, Staff and Student Publications

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.

OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR …

Identification Of Bradycardia Following Remdesivir Administration Through The Us Food And Drug Administration American College Of Medical Toxicology Covid-19 Toxic Pharmacovigilance Project, Jason M Devgun, Rongmei Zhang, Jeffrey Brent, Paul Wax, Keith Burkhart, Alison Meyn, Sharan Campleman, Stephanie Abston, Kim Aldy

Faculty, Staff and Student Publications

IMPORTANCE: The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion-associated AE listed in the US Food and Drug Administration-approved prescribing information.

OBJECTIVE: To evaluate the magnitude and duration of bradycardic events following remdesivir administration.

DESIGN, SETTING, AND PARTICIPANTS: A multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 …

Pyridoxamine Treatment Ameliorates Large Artery Stiffening And Cerebral Artery Endothelial Dysfunction In Old Mice, Emily H Reeve, Elise K Kronquist, Julia R Wolf, Byron Lee, Aleena Khurana, Hanson Pham, Abigail E Cullen, Jessica A Peterson, Antonio Meza, R Colton Bramwell, Laura Villasana, Daniel R Machin, Grant D Henson, Ashley E Walker

Faculty, Staff and Student Publications

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old …

Association Of Metformin With The Development Of Age-Related Macular Degeneration, Amitha Domalpally, Samuel A Whittier, Qing Pan, Dana M Dabelea, Christine H Darwin, William C Knowler, Christine G Lee, Jose A Luchsinger, Neil H White, Emily Y Chew

Faculty, Staff and Student Publications

IMPORTANCE: Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD.

OBJECTIVE: To investigate the association between metformin use and age-related macular degeneration (AMD).

DESIGN, SETTING, AND PARTICIPANTS: The Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for …

Association Of Frailty And The Expanded Operative Stress Score With Preoperative Acute Serious Conditions, Complications, And Mortality In Males Compared To Females: A Retrospective Observational Study, Qi Yan, Jeongsoo Kim, Daniel E Hall, Myrick C Shinall, Katherine Moll Reitz, Karyn B Stitzenberg, Lillian S Kao, Elizabeth L George, Ada Youk, Chen-Pin Wang, Jonathan C Silverstein, Elmer V Bernstam, Paula K Shireman

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to expand Operative Stress Score (OSS) increasing procedural coverage and assessing OSS and frailty association with Preoperative Acute Serious Conditions (PASC), complications and mortality in females versus males.

SUMMARY BACKGROUND DATA: Veterans Affairs male-dominated study showed high mortality in frail veterans even after very low stress surgeries (OSS1).

METHODS: Retrospective cohort using NSQIP data (2013-2019) merged with 180-day postoperative mortality from multiple hospitals to evaluate PASC, 30-day complications and 30-, 90-, and 180-day mortality.

RESULTS: OSS expansion resulted in 98.2% case coverage versus 87.0% using the original. Of 82,269 patients (43.8% male), 7.9% …

Assessment Of Symptom, Disability, And Financial Trajectories In Patients Hospitalized For Covid-19 At 6 Months, Andrew J Admon, Theodore J Iwashyna, Lee A Kamphuis, Stephanie J Gundel, Sarina K Sahetya, Ithan D Peltan, Steven Y Chang, Jin H Han, Kelly C Vranas, Kirby P Mayer, Aluko A Hope, Sarah E Jolley, Ellen Caldwell, Max L Monahan, Katrina Hauschildt, Samuel M Brown, Neil R Aggarwal, B Taylor Thompson, Catherine L Hough

Faculty, Staff and Student Publications

IMPORTANCE: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited.

OBJECTIVE: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization.

DESIGN, SETTING, AND PARTICIPANTS: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization …

Gender Bias In The Evaluation Of Surgical Performance: Results Of A Prospective Randomized Trial, Mara B Antonoff, Hope Feldman, Jessica G Y Luc, Paula I Iaeger, M Laura Rubin, Liang Li, Ara A Vaporciyan

Faculty, Staff and Student Publications

Objective: The study aims to determine the influence of trainee gender on assessments of coronary anastomosis performance.

Summary of background data: Understanding the impact of gender bias on the evaluation of trainees may enable us to identify and utilize assessment tools that are less susceptible to potential bias.

Methods: Cardiothoracic surgeons were randomized to review the video performance of trainees who were described by either male or female pronouns. All participants viewed the same video of a coronary anastomosis and were asked to grade technique using either a Checklist or Global Rating Scale (GRS). Effect of trainee gender on scores …

Factors And Behaviors Related To Successful Transition Of Care After Hospitalization For Ischemic Stroke, Chuanhui Dong, Hannah Gardener, Tatjana Rundek, Erika Marulanda, Carolina M Gutierrez, Iszet Campo-Bustillo, Gillian Gordon Perue, Karlon H Johnson, Ralph L Sacco, Jose G Romano, Transitions Of Care Stroke Disparities Study (Tcsd-S) Investigators

Faculty, Staff and Student Publications

BACKGROUND: Our objective is to describe adoption of the posthospitalization behaviors associated with successful transition of care and related baseline characteristics.

METHODS: This study includes 550 participants in the Transition of Care Stroke Disparities Study, a prospective observational cohort derived from the Florida Stroke Registry. Participants had an ischemic stroke (2018-2021), discharged home or to rehabilitation, with modified Rankin Scale score=0-3 (44% women, 24% Black, 48% White, 26% Hispanic, 35% foreign-born). We collected baseline sociodemographic and clinical characteristics. A structured telephone interview at 30-day postdischarge evaluated outcomes including medication adherence, medical appointment attendance, outpatient therapy, exercise, diet modification, toxic habit …

Adverse Pregnancy Outcomes And Long Term Risk Of Ischemic Heart Disease In Mothers: National Cohort And Co-Sibling Study, Casey Crump, Jan Sundquist, Mary Ann Mclaughlin, Siobhan M Dolan, Usha Govindarajulu, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers.

DESIGN: National cohort study.

SETTING: Sweden.

PARTICIPANTS: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015.

MAIN OUTCOME MEASURES: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy …

Circulation Of Rhinoviruses And/Or Enteroviruses In Pediatric Patients With Acute Respiratory Illness Before And During The Covid-19 Pandemic In The Us., Danielle A. Rankin, Andrew J. Spieker, Ariana Perez, Anna L. Stahl, Herdi K. Rahman, Laura S. Stewart, Jennifer E. Schuster, Joana Y. Lively, Zaid Haddadin, Varvara Probst, Marian G. Michaels, John V. Williams, Julie A. Boom, Leila C. Sahni, Mary A. Staat, Elizabeth P. Schlaudecker, Monica M. Mcneal, Christopher J. Harrison, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Susan I. Gerber, Meredith Mcmorrow, Brian Rha, James D. Chappell, Rangaraj Selvarangan, Claire M. Midgley, Natasha B. Halasa, Nvsn Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting.

OBJECTIVE: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought …

Structural Valve Deterioration After Self-Expanding Transcatheter Or Surgical Aortic Valve Implantation In Patients At Intermediate Or High Risk., Daniel O'Hair, Steven J Yakubov, Kendra J Grubb, Jae K Oh, Saki Ito, G Michael Deeb, Nicolas M Van Mieghem, David H Adams, Tanvir Bajwa, Neal S Kleiman, Stanley Chetcuti, Lars Søndergaard, Hemal Gada, Mubashir Mumtaz, John Heiser, William M Merhi, George Petrossian, Newell Robinson, Gilbert H L Tang, Joshua D Rovin, Stephen H Little, Renuka Jain, Sarah Verdoliva, Tim Hanson, Shuzhen Li, Jeffrey J Popma, Michael J Reardon

Heart and Vascular Articles

IMPORTANCE: The frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood.

OBJECTIVE: To evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve …

Why Does The X Chromosome Lag Behind Autosomes In Gwas Findings?, Ivan P Gorlov, Christopher I Amos

Faculty, Staff and Students Publications

The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used data from the Catalog of Published Genome Wide Association Studies to compare densities of the GWAS-detected SNPs on the X-chromosome and autosomes. The density of GWAS-detected SNPs on the X-chromosome is 6-fold lower compared to the density of the GWAS-detected SNPs on autosomes. Differences between the X-chromosome and autosomes cannot be explained by differences in the overall SNP density, lower X-chromosome coverage …

Anxiety Sensitivity And Cigarette Use On Cannabis Use Problems, Perceived Barriers For Cannabis Cessation, And Self-Efficacy For Quitting Among Adults With Cannabis Use Disorder, Michael F Orr, Luke F Heggeness, Nirvi Mehta, Jacob Moya, Kara Manning, Lorra Garey, Julianna Hogan, Marcel De Dios, Michael J Zvolensky

Faculty, Staff and Students Publications

Many individuals diagnosed with cannabis use disorder (CUD) report a desire to quit using cannabis due to problems associated with use. Yet, successful abstinence is difficult for a large subset of this population. Thus, the present study sought to elucidate potential risk factors for cannabis use problems, perceived barriers for quitting, and diminished self-efficacy for remaining abstinent. Specifically, this investigation examined cigarette user status, anxiety sensitivity, and the interplay between these individual difference factors in terms of cannabis-related problems, perceived barriers for cannabis cessation, and self-efficacy for quitting cannabis use. The sample consisted of 132 adult cannabis users who met …

Comparison Of Postoperative Outcomes Of Laparoscopic Vs Open Inguinal Hernia Repair, Jennie Meier, Audrey Stevens, Miles Berger, Konstantinos I Makris, Athanasios Bramos, Joan Reisch, C Munro Cullum, Simon C Lee, Celette Sugg Skinner, Herbert Zeh, Cynthia J Brown, Courtney J Balentine

Faculty, Staff and Students Publications

Importance: Advocates of laparoscopic surgery argue that all inguinal hernias, including initial and unilateral ones, should be repaired laparoscopically. Prior work suggests outcomes of open repair are improved by using local rather than general anesthesia, but no prior studies have compared laparoscopic surgery with open repair under local anesthesia.

Objective: To evaluate postoperative outcomes of open inguinal hernia repair under general or local anesthesia compared with laparoscopic repair.

Design, setting, and participants: This retrospective cohort study identified 107 073 patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent unilateral initial inguinal hernia repair from 1998 to 2019. …

Current Challenges And Future Direction In Surveillance For Hepatocellular Carcinoma In Patients With Nonalcoholic Fatty Liver Disease, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related …

Lumasiran For Advanced Primary Hyperoxaluria Type 1: Phase 3 Illuminate-C Trial, Mini Michael, Jaap W Groothoff, Hadas Shasha-Lavsky, John C Lieske, Yaacov Frishberg, Eva Simkova, Anne-Laure Sellier-Leclerc, Arnaud Devresse, Fitsum Guebre-Egziabher, Sevcan A Bakkaloglu, Chebl Mourani, Rola Saqan, Richard Singer, Richard Willey, Bahru Habtemariam, John M Gansner, Ishir Bhan, Tracy Mcgregor, Daniella Magen

Faculty, Staff and Students Publications

Rationale & objective: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.

Study design: Phase 3, open-label, single-arm trial.

Setting & participants: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age < 12 months), and POx ≥20 μmol/L at screening, including patients with or without systemic oxalosis.

Intervention: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing.

Outcome: Primary end point: percent change in POx …

Functional And Clinical Studies Reveal Pathophysiological Complexity Of Clcn4-Related Neurodevelopmental Condition, Elizabeth E Palmer, Michael Pusch, Alessandra Picollo, Caitlin Forwood, Matthew H Nguyen, Vanessa Suckow, Jessica Gibbons, Alva Hoff, Lisa Sigfrid, Andre Megarbane, Mathilde Nizon, Benjamin Cogné, Claire Beneteau, Fowzan S Alkuraya, Aziza Chedrawi, Mais O Hashem, Hannah Stamberger, Sarah Weckhuysen, Arnaud Vanlander, Berten Ceulemans, Sulekha Rajagopalan, Kenneth Nunn, Stéphanie Arpin, Martine Raynaud, Constance S Motter, Catherine Ward-Melver, Katrien Janssens, Marije Meuwissen, Diane Beysen, Nicola Dikow, Mona Grimmel, Tobias B Haack, Emma Clement, Amy Mctague, David Hunt, Sharron Townshend, Michelle Ward, Linda J Richards, Cas Simons, Gregory Costain, Lucie Dupuis, Roberto Mendoza-Londono, Tracy Dudding-Byth, Jackie Boyle, Carol Saunders, Emily Fleming, Salima El Chehadeh, Marie-Aude Spitz, Amelie Piton, Bénédicte Gerard, Marie-Thérèse Abi Warde, Gillian Rea, Caoimhe Mckenna, Sofia Douzgou, Siddharth Banka, Cigdem Akman, Jennifer M Bain, Tristan T Sands, Golder N Wilson, Erin J Silvertooth, Lauren Miller, Damien Lederer, Rani Sachdev, Rebecca Macintosh, Olivier Monestier, Deniz Karadurmus, Felicity Collins, Melissa Carter, Luis Rohena, Marjolein H Willemsen, Charlotte W Ockeloen, Rolph Pfundt, Sanne D Kroft, Michael Field, Francisco E R Laranjeira, Ana M Fortuna, Ana R Soares, Vincent Michaud, Sophie Naudion, Sailaja Golla, David D Weaver, Lynne M Bird, Jennifer Friedman, Virginia Clowes, Shelagh Joss, Laura Pölsler, Philippe M Campeau, Maria Blazo, Emilia K Bijlsma, Jill A Rosenfeld, Christian Beetz, Zöe Powis, Kirsty Mcwalter, Tracy Brandt, Erin Torti, Mikaël Mathot, Shekeeb S Mohammad, Ruth Armstrong, Vera M Kalscheuer

Faculty, Staff and Students Publications

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on …

Effects Of Alginate Oligosaccharide On Testosterone-Induced Benign Prostatic Hyperplasia In Orchiectomized Rats, You-Jee Jang, Hye-Yeon Jung, Ju-Yeong Myeong, Kwang Hoon Song, Joseph Kwon, Duwoon Kim, Jae-Il Park

Faculty, Staff and Student Publications

Benign prostatic hyperplasia (BPH) is an age-related disease of the urinary system that affects elderly men. Current treatments for BPH are associated with several adverse effects, thus highlighting the need for alternative agents. Alginate oligosaccharide (AOS), a water-soluble functional oligomer derived from brown algae, inhibits prostate cancer cell proliferation. However, the effects of AOS on BPH and the underlying molecular mechanisms remain unclear. Therefore, here, we aimed to investigate the therapeutic potential of AOS in BPH by using human benign prostatic epithelial cells (BPH-1) and a rat model of testosterone-induced BPH. Treatment with AOS inhibited in vitro and in vivo …

A Survey With Interventional Components Delivered On Tablet Devices Versus Usual Care To Increase Pre-Exposure Prophylaxis Uptake Among Cisgender Black Women: A Pilot Randomized Controlled Trial, Mandy J Hill, Angela M Heads, Robert Suchting, Angela L Stotts

Faculty, Staff and Student Publications

BACKGROUND: Cisgender (cis) Black women in the USA are more likely to become HIV positive during their lifetime than other women. We developed and implemented a behavioral intervention, Increasing PrEP (iPrEP), the first pilot randomized controlled trial (RCT) aimed at motivating cis Black women to be willing to use PrEP for HIV prevention and attend an initial PrEP clinic visit following an emergency department visit.

METHODS: Eligible participants were Black cisgender women ages 18-55 years who acknowledged recent condomless sex and substance use. Participants were randomized to iPrEP or usual care (UC). iPrEP is a survey-based intervention designed to raise …

Examining Stripes On A Herd Of Zebras: Impact Of Genomic Matching For Ultrarare Sarcomas In Phase 1 Clinical Trials (Samba 102), Justin T Moyers, Roberto Carmagnani Pestana, Jason Roszik, David S Hong, Aung Naing, Siqing Fu, Sarina Piha-Paul, Timothy A Yap, Daniel Karp, Jordi Rodon, Andy Livingston, Maria Alejandra Zarzour, Vinod Ravi, Shreyaskumar Patel, Robert S Benjamin, Joseph Ludwig, Cynthia Herzog, Ravin Ratan, Neeta Somaiah, Anthony Conley, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Recently, the Connective Tissue Oncology Society published consensus guidelines for recognizing ultrarare sarcomas (URS), defined as sarcomas with an incidence ≤1 per 1,000,000. We assessed the outcomes of 56 patients with soft tissue, and 21 with bone sarcomas, enrolled in Phase 1 trials.

Experimental design: In this Sarcoma-Matched Biomarker Analysis (SAMBA-102 study), we reviewed records from patients on Phase 1 trials at the University of Texas MD Anderson Cancer Center between January 2013 and June 2021.

Results: Among 587 sarcomas, 106 (18.1%) were classified as URS. Fifty (47%) were male, and the median age was 44.3 years (range, 19-82). …

Physical Activity, Seasonal Sensitivity And Psychological Well-Being Of People Of Different Age Groups Living In Extreme Environments, Caren Alvarado, Matías Castillo-Aguilar, Valeska Villegas, Claudia Estrada Goic, Katherine Harris, Patricio Barria, Michele M Moraes, Thiago T Mendes, Rosa M E Arantes, Pablo Valdés-Badilla, Cristian Núñez-Espinosa

Faculty, Staff and Student Publications

Physical activity can prevent many organic and mental pathologies. For people living in extreme southern high-latitude environments, weather conditions can affect these activities, altering their psychological well-being and favoring the prevalence of seasonal sensitivity (SS). This study aims to determine the relationships between the practice of physical activity, seasonal sensitivity and well-being in people living in high southern latitudes. A cross-sectional study was conducted, using the Seasonal Pattern Assessment Questionnaire (SPAQ), applying a psychological well-being scale, and determining sports practice according to the recommendations of the World Health Organization (WHO) for the 370 male (n = 209; 55%) and female …

Planarians To Schistosomes: An Overview Of Flatworm Cell-Types And Regulators, J Lee

Faculty, Staff and Student Publications

Schistosomiasis remains a major neglected tropical disease that afflicts over 200 million people globally. Schistosomes, the aetiological agent of schistosomiasis, are parasitic flatworms that propagate between molluscan and mammalian hosts. Inside the mammalian host, schistosomes rapidly grow over 100-fold in size and develop into a sexually mature male or female that thrives in the bloodstream for several decades. Recent work has identified schistosome stem cells as the source that drives parasite transmission, reproduction and longevity. Moreover, studies have begun to uncover molecular programmes deployed by stem cells that are essential for tissue development and maintenance, parasite survival and immune evasion. …

Clonal Hematopoiesis And Risk Of Prostate Cancer In Large Samples Of European Ancestry Men, Anqi Wang, Yili Xu, Yao Yu, Kevin T Nead, Taebeom Kim, Keren Xu, Tokhir Dadaev, Ed Saunders, Xin Sheng, Peggy Wan, Loreall Pooler, Lucy Y Xia, Stephen Chanock, Sonja I Berndt, Susan M Gapstur, Victoria Stevens, Demetrius Albanes, Stephanie J Weinstein, Vincent Gnanapragasam, Graham G Giles, Tu Nguyen-Dumont, Roger L Milne, Mark M Pomerantz, Julie A Schmidt, Konrad H Stopsack, Lorelei A Mucci, William J Catalona, Kurt N Hetrick, Kimberly F Doheny, Robert J Macinnis, Melissa C Southey, Rosalind A Eeles, Fredrik Wiklund, Zsofia Kote-Jarai, Adam J De Smith, David V Conti, Chad Huff, Christopher A Haiman, Burcu F Darst

Faculty, Staff and Student Publications

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not …

Prospective Association Of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis, Amanda E Paluch, Shivangi Bajpai, Marcel Ballin, David R Bassett, Thomas W Buford, Mercedes R Carnethon, Ariel Chernofsky, Erin E Dooley, Ulf Ekelund, Kelly R Evenson, Deborah A Galuska, Barbara J Jefferis, Lingsong Kong, William E Kraus, Martin G Larson, I-Min Lee, Charles E Matthews, Robert L Newton, Anna Nordström, Peter Nordström, Priya Palta, Alpa V Patel, Kelley Pettee Gabriel, Carl F Pieper, Lisa Pompeii, Erika Rees-Punia, Nicole L Spartano, Ramachandran S Vasan, Peter H Whincup, Shengping Yang, Janet E Fulton, Steps For Health Collaborative

Faculty, Staff and Students Publications

Background: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines.

Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional …

A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Atrayee Basu Mallick, Nora K Horick, Andrea Wang-Gillam, Peter Joel Hosein, Michael A Morse, Muhammad Shaalan Beg, Janet E Murphy, Sharon Mavroukakis, Anjum Zaki, Benjamin L Schlechter, Hanna Sanoff, Christopher Manz, Brian M Wolpin, Philip Arlen, Jill Lacy, James M Cleary

Department of Medical Oncology Faculty Papers

Importance: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

Objective: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

Design, setting, and participants: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer, Thirumagal Thiyagarajan, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Sarah Asemota, Kirsten L Young, Daniel L Johnson, Vera Bocharova, Weidong Zhou, Abhinav K Jain, Emanuel F Petricoin, Zheng Yin, Lawrence M Pfeffer, Duane D Miller, Ramesh Narayanan

Faculty, Staff and Student Publications

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a …